(a) Field of the Invention
This invention relates to selected 3,4-dihydro-5-(pyridinyl or phenyl)-2(1H)-pyridinones, their use as cardiotonics, their preparation and intermediates therefor.
(b) Description of the Prior Art
Shen et al [U.S. Pat. No. 3,718,743, issued Feb. 27, 1973] show "5-phenyl-2-piperidinones and 5-phenyl-2-thiopiperidinones in compositions and methods for treating pain, fever and inflammation". The generic teaching of these piperidinones shows that "phenyl" can have one or two substituents at positions 2, 3, 4, 5 and/or 6, including alkyl, halogen, haloalkyl, aryl, nitro, amino, acylamino, acyl, carboxy, carbalkoxy, carbamyl, dialkylsulfamyl, alkylamino, dialkylamino, alkylmercapto, alkylsulfinyl and alkylsulfonyl. Various means of preparing the 5-phenyl-2-piperidinone final products are shown. In one procedure, a 2-chloro-5-phenylpyridine was heated with aqueous sodium hydroxide in dimethylformamide to produce the corresponding 5-phenyl-2(1H)-pyridinones which were then hydrogenated to produce the desired 5-phenyl-2-piperidinones. Among the intermediate 5-phenyl-2(1H)-pyridinones specifically shown is 5-(4-hydroxyphenyl)-2(1H)-pyridinone as well as its preparation by heating the corresponding 5-(4-methoxyphenyl)-2(1H)-pyridinone with pyridine hydrochloride under nitrogen.
Lesher and Opalka [U.S. Pat. Nos. 4,004,012, issued Jan. 18, 1977, and 4,072,746, issued Feb. 7, 1978] show inter alia, as cardiotonic agents 5-(pyridinyl)-2(1H)-pyridinones and their preparation by decarboxylating the corresponding 3-carboxy compounds. The disclosure of U.S. Pat. No. 4,072,746 also is shown in Lesher and Opalka U.S. Pat. Nos. 4,107,315, 4,137,233, 4,199,586 and 4,225,715.
Lesher, Opalka and Page [U.S. Pat. No. 4,312,875, issued Jan. 26, 1982] show, inter alia, as cardiotonic agents 5-(pyridinyl)-6-(lower-alkyl)-2(1H)-pyridinones and their preparation by decarboxylating the corresponding 3-carboxy compounds.